The field of this invention is nucleic acid arrays.
xe2x80x9cBiochipsxe2x80x9d or arrays of binding agents, such as oligonucleotides and peptides, have become an increasingly important tool in the biotechnology industry and related fields. These binding agent arrays, in which a plurality of binding agents are deposited onto a solid support surface in the form of an array or pattern, find use in a variety of applications, including gene expression analysis, drug screening, nucleic acid sequencing, mutation analysis, and the like.
Such arrays may be prepared in a number of different ways. For example, DNA arrays may be prepared manually by spotting DNA onto the surface of a substrate with a micro pipette. See Khrapko et al., DNA Sequence (1991) 1:375-388. Alternatively, the dot-blot approach, as well as the derivative slot-blot approach, may be employed in which a vacuum manifold transfers aqueous DNA samples from a plurality of wells to a substrate surface. In yet another method of producing arrays of biopolymeric molecules, a pin is dipped into a fluid sample of the biopolymeric compound and then contacted with the substrate surface. By using a plurality or array of pins, one can transfer a plurality of samples to the substrate surface at the same time. Alternatively, an array of capillaries can be used to produce biopolymeric arrays. See WO 95/35505. In another method of producing biopolymeric arrays, arrays of biopolymeric agents are xe2x80x9cgrownxe2x80x9d on the surface of a substrate in discreet regions. See e.g. U.S. Pat. No. 5,143,854 and Fodor et al., Science (1991) 251:767-773. In yet another method of producing nucleic acid arrays, piezo inkjets are used to deposit nucleic acids on the surface of a substrate. See U.S. Pat. No. 5,658,802. However, the U.S. Pat. No. 5,658,802 patent states that with regard to thermal inkjet devices, xe2x80x9c[t ]hermal ink jets, however, are very stressful on the dispensed fluid and the fluid must not be too aggressive to the heater element. Because of these constraints, thermal ink jets are generally unsuitable for dispensing applications other than those where the composition of the ink can be fully controlled.xe2x80x9d Col. 2, lines 14 to 19. Each of the above methods of producing arrays has certain disadvantages, e.g. complexity, non-reproducibility, etc.
Accordingly, there is continued interest in the development of new methods and devices for producing biopolymeric arrays. Of particular interest would be the development of a method for rapidly producing a nucleic acid array in which a minimal amount of the nucleic acid sample is used to produce reproducible nucleic acid spots.
Patents and patent applications describing arrays of biopolymeric compounds and methods for their fabrication include: U.S. Pat. Nos. 5,242,974; 5,384,261; 5,405,783; 5,412,087; 5,424,186; 5,429,807; 5,436,327; 5,445,934; 5,472,672; 5,527,681; 5,529,756; 5,545,531; 5,554,501; 5,556,752; 5,561,071; 5,599,695; 5,624,711; 5,639,603; 5,658,734; WO 93/17126; WO 95/11995; WO 95/35505; EP 742 287; and EP 799 897.
Other references of interest include: Lockhart et al., Nature Biotechnology (1996) 14: 1675-1680; Schena et al., Science (1995) 270: 467-470; Schena et al., Proc. Nat""l Acad. Sci. USA (1996)93:10614-10619; Shalon et al., Genome Res. (1996) 6: 639-645; Milosavljevic et al., Genome Res. (1996) 6:132-141; Nguyen et al., Genomics (1995)29: 207-216; Pixc3xa9tu et al., Genome Res. (1996) 6: 492-503; Zhao et al., Gene (1995) 166:207-213; Chalifour et al., Anal. Biochem. (1994) 216:299-304; Heller et al., Proc. Nat""l Acad. Sci. USA (1997) 94: 2150-2155; Khrapko et al., DNA Sequence (1991) 1:375-388; Lehrach et al., Hybridization Fingerprinting in Genome Mapping and Sequencing, Genome Analysis, Vol. 1 (Davies and Tilgham, eds)(Cold Spring Harbor Press) (1990) pp 39-81; Schema, M., BioAssays (1996) 18: 427-431; DeRisi et al., Nat. Genet. (1996) 14457-460; DeRisi et al., Science (1997) 278: 680-686; and Chen et al., Biomedical Optics (1997) 2: 364-374.
U.S. Patents disclosing the use of inkjet devices to dispense bio/chemical agents such as proteins and nucleic acids include: U.S. Pat. Nos. 4,877,745; 5,338,688; 5,474,796; 5,449,754; 5,658,802; and 5,700,637.
Methods and devices for depositing nucleic acids on a substrate surface are provided. In the subject methods, a thermal inkjet head loaded with fluid composition of the nucleic acid is positioned in opposing relationship to, e.g. over, a substrate surface. The thermal inkjet head is then actuated in a manner sufficient to expel a volume of the aqueous nucleic acid composition onto the substrate surface. The subject methods and devices find use in a variety of applications, particularly in the preparation of nucleic acid arrays, including arrays of oligonucleotides and polynucleotides, e.g. cDNA arrays.